Dose Of Cabergoline Research Articles

Effect of Cabergoline on Metabolism in Prolactinomas

Introduction: Hyperprolactinemia has been implicated in the pathogenesis of obesity and glucose intolerance and is reportedly associated with an impaired metabolic profile. The current study aimed at investigating the effects of 12- and 60-month treatment with cabergoline (CAB) on metabolic syndrome (MetS) in patients with prolactinomas. Patients and Methods: 61 patients with prolactinomas (13 men, 48 women, 41 with microadenoma, 20 with macroadenoma), aged 34.4 ± 10.3 years, entered the study. In all patients, prolactin (PRL) and metabolic parameters were assessed at diagnosis and after 12 and 60 months of continuous CAB treatment. MetS was diagnosed according to NCEP-ATP III criteria. Results: Compared to baseline, CAB induced a significant decrease in PRL with complete normalization in 93% of patients after the 60-month treatment. At baseline, MetS prevalence was significantly higher in patients with PRL above (34.5%) than in those with PRL lower (12.5%) than the median (129 μg/l, p = 0.03). MetS prevalence significantly decreased after 12 (11.5%, p = 0.039) and 60 (5.0%, p = 0.001) months compared to baseline (28.0%). At both evaluations the lipid profile significantly improved compared to baseline. Fasting insulin and homeostatic model assessment of insulin resistance significantly decreased after 1 year of CAB (p = 0.012 and p = 0.002, respectively) and further improved after 60 months (p = 0.000). The visceral adiposity index significantly decreased after the 60-month treatment (p = 0.000) compared to baseline. At the 5-year evaluation CAB dose was the best predictor of percent decrease in fasting insulin (t = 2.35, p = 0.022). Conclusions: CAB significantly reduces MetS prevalence and improves the adipose tissue dysfunction index. The improvement in PRL, insulin sensitivity and other metabolic parameters might reflect the direct effect of CAB.

Second attempt to withdraw cabergoline in prolactinomas: a pilot study

According to Pituitary and Endocrine Society recommendations, cabergoline (CAB) therapy can be discontinued after 2 years in hyperprolactinemic patients who fit certain criteria. Previous studies found recurrence rates ranging between 26 and 69 %. Whether CAB therapy can be successfully discontinued after one unsuccessful withdrawal is unknown. We conducted a pilot prospective two-center study on a second attempt of CAB withdrawal. Inclusion criteria were: (1) recurrence of hyperprolactinemia after first withdrawal; (2) additional CAB therapy for at least 2 years; (3) normal serum prolactin; (4) CAB dose ≤ 1 mg/week. Prolactin level was monitored after discontinuing therapy. Median follow up for patients who are still in remission was 42 months (range = 24-60). A total of 17 patients were recruited. Mean age was 41.0 ± 17.3 years. 65 % were female. Initial tumors were microadenoma in 64.7 %, and macroadenoma in 35.3 %. The average weekly CAB dose at second withdrawal was 0.38 ± 0.20 mg (median = 0.25, range = 0.175-1). Eleven of 17 patients (64.7 %) recurred. Median time to recurrence was 6 months. The incidence of recurrence was 44 events per 100 person-years. The estimated cumulative hazard of recurrence was 40 and 82 % at 6 and 12 months respectively. The probability to be recurrence-free at 6 and 12 months was 65 and 41 %, respectively. Second attempt of CAB withdrawal after 2 additional years of therapy may be successful in some patients. A second withdrawal can be attempted with close monitoring of prolactin level. In this study, we could not identify any predictor of recurrence. Most of the recurrences occurred within the first 12 months after withdrawal.

Remission with Cabergoline in Adolescent Boys with Cushing’s Disease

Cabergoline is a long-acting dopamine receptor agonist used for treatment of patients with uncured Cushing’s disease (CD) and, as a first-line treatment, was used in only limited numbers of patients. This report presents two adolescent boys with CD who were treated with cabergoline. Two adolescent boys with clinical and laboratory findings of CD are presented. No pituitary adenoma was detected by radiological investigation in either patient. Adrenocorticotropic hormone (ACTH) hypersecretion and lateralization was found by inferior petrosal sinus sampling in both patients. The initial cabergoline dose was 1mg/week and was adjusted up to 1.5 mg/week in the second patient, based on his urinary free cortisol (UFC) level. The patients responded to cabergoline treatment with normal UFC levels on the 4th and 6th months of treatment. The boys reached complete remission at the end of the 17th and 24th months, respectively. Cabergoline is effective in the control of cortisol secretion and can be considered as a first-line treatment in cases of CD. Conflict of interest:None declared.

Treatment of antipsychotic-induced hyperprolactinemia with bromocriptine: A case report

INTRODUCTION Previous literature has highlighted an increase in morbidity and mortality associated with antipsychotic use in persons with severe mental illnesses (SMI), which include schizophrenia and bipolar disorder. Drug-induced hyperprolactinemia is a function of dopamine blockade in the anterior pituitary. Elevated prolactin levels are often accompanied by symptoms of decreased libido and erectile dysfunction (ED) in men, and galactorrhea and amenorrhea in women. However, the extent to which antipsychotic (AP) use is associated with sexual dysfunction has not been extensively reported. Hyperprolactinemia may also increase the risk for osteopenia.

Effects of cabergoline on hyperprolactinemia, psychopathology, and sexual functioning in schizophrenic patients.

Antipsychotic medications are associated to different degrees with sexual dysfunction mainly through their potential to induce hyperprolactinemia. Prolactin (PRL) secretion is mainly regulated by the hypothalamic dopaminergic systems. We conducted this 6-month, parallel-group study to prospectively investigate the effects of the dopamine agonist cabergoline on sexual dysfunction in clinically stable patients with schizophrenia (DSM-IV, AP 194) and hyperprolactinemia (PRL > 20 ng/ml for men and PRL > 25 ng/ml for women). In total 80 patients were enrolled; 33 were receiving risperidone, 17 haloperidol, 11 amisulpride, and 8 risperidone microspheres long acting. Based on PRL levels (< 50, 50-99, or > 100 ng/ml), patients were assigned in 3 cabergoline doses (0.25, 0.5, and 1 mg/day in 38, 23, and 19 patients, respectively). The psychopathology was evaluated using the Positive and Negative Syndrom Scale (PANSS), and sexual dysfunction was evaluated using the Arizona Sexual Experiences Scale (ASEX). PRL levels were reduced in all patients, from 73.3 (± 46.8) to 42.0 (± 27.8) at Month 3 and 27.1 (± 20.4) at Month 6 (p < .001). ASEX scores declined from 19.1 (± 5.1) to 17.6 (± 5.5) at Month 3 and 15.0 (± 6.5) at Month 6 (p < .001). PANSS scores were reduced in the third and in the sixth month (p = .001 at 6 month vs. baseline). The decrease in PRL was not statistically different between groups. Our data suggest that cabergoline administration to clinically stable patients with schizophrenia may improve sexual functioning without adversely affecting their psychopathologic status, provided that the dose has been suited to the severity of the hyperprolactinemia.

Index of Suspicion

* ALT: : alanine aminotransferase AST: : aspartate aminotransferase BUN: : blood urea nitrogen CBC: : complete blood count CNS: : central nervous system CSF: : cerebrospinal fluid CT: : computed tomography ECG: : electrocardiography ED: : emergency department EEG: : electroencephalography ESR: : erythrocyte sedimentation rate GI: : gastrointestinal GU: : genitourinary Hct: : hematocrit Hgb: : hemoglobin MRI: : magnetic resonance imaging WBC: : white blood cell An 11-year-old boy presents to the emergency department with a 1-week history of frequent episodes of nonbloody, nonbilious emesis associated with diarrhea and abdominal cramping. He has urgency and fecal incontinence. He has been afebrile and denies any rashes, joint pain, sick contacts, headaches, or other symptoms. On further questioning, his mother reveals that he has had 2 similar episodes of abdominal distension and diarrhea during the past 6 to 7 years. Between these episodes, she states that he normally has nonbloody, hard stools accompanied by straining and chronic abdominal pain and pain with defecation. When asked specifically, his mother does not remember when he passed his first stool after he was born. On physical examination, his temperature is 37.6°C, pulse is 100 beats per minute, respiratory rate is 16 breaths per minute, blood pressure is 113/62 mm Hg, oxygen saturation is 100% on room air, height is 63 inches (95%), and weight is 36.7 kg (25%). He has abdominal distention and diffuse abdominal tenderness with voluntary guarding. There is palpable stool in the left quadrant. There is no perianal erythema or skin tag, and rectal examination reveals a low anal tone. A CT scan of the abdomen (Figure 1) reveals a markedly distended rectosigmoid colon with circumferential, confluent, and contiguous mural thickening. Basic metabolic profile, CBC, and urinalysis results are unremarkable, but the C-reactive protein level is elevated at 131 mg/L (1248 nmol/L). Because of the concern for enterocolitis, he is empirically given broad-spectrum intravenous antibiotics and transferred to a children’s hospital for further evaluation. Figure 1. A CT scan of the abdomen shows a markedly distended rectosigmoid colon with circumferential mural thickening. A 4-year-old boy presents for evaluation of intermittent fevers of 4 weeks’ duration after 2 separate antibiotic courses prescribed for acute otitis media. He has experienced clear rhinorrhea and …

Effects of Cabergoline administration on uterine perfusion in women with polycystic ovary syndrome

The aim of this study was to determine the effects of Cabergoline administration on uterine blood flow in women suffering from polycystic ovary syndrome (PCOS). This study is a randomized, controlled, triple-blind trial which is tested on 40 women who were randomly divided into two groups of 20 people and using arandomized blockdesign during which the subjects were assessed and included. They were suffering from polycystic ovarian syndrome. Inclusion criteria were classically defined PCOS criteria including: oligomenorrhea or amenorrhea, clinical or Laboratory findings based on increase in blood level androgen (testosterone) and ultrasound confirmation of PCOS. Exclusion criteria were Pregnancy, lactation, Dopamine Agonist Therapy. After selection of intervention and placebo groups, primary control Doppler ultrasound was done for both groups. Then a weekly dose of Cabergoline 0.5 mg was administered to intervention group for duration of 12 weeks. Placebo group were administered placebo in the same fashion. At the end of 12 weeks, Doppler ultrasound was performed and the results were recorded in the check lists. No significant difference was noticed in both groups with respect to their age, employment, level of education, type of infertility, duration of marriage, and results of RI and PI before intervention. Later PCOS patients under the treatment of Cabergoline showed a significant increase in uterine blood flow Pulsatility Index (PI) before 2.65±0.52 and after 1.98±0.52 and RI before 0.85 and after intervention 0.77), yet no significant difference were found in PCOS patient under the treatment of placebo. PCOS patients were shown to have more resistance in uterine blood flow than healthy people; however, Cabergoline administration proved to increase uterine blood perfusion and regulate menstruation cycle.

Comparative efficacy of various therapeutic protocols in the treatment of pyometra in bitches

This study was undertaken on canine pyometra and consisted of 28 bitches of different breeds with known breeding history and open type of pyometra. The diagnosis of pyometra was made by correlating the history and clinical signs with the findings of abdominal palpation, radiography and ultrasonography. The physiological, haematological and biochemical parameters were evaluated before and at the end of therapy. The clinical cases were divided randomly into four different groups with each group consisting of seven bitches. One untreated control group in which bitches were given only supportive therapies was included. The bitches in the other three groups were treated using natural PGF&lt;sub&gt;2&lt;/sub&gt;&amp;alpha; or synthetic PGF&lt;sub&gt;2&lt;/sub&gt;&amp;alpha; or a combination of a dopamine agonist prolactin-inhibiting drug, i.e., cabergoline and lower dose of synthetic PGF&lt;sub&gt;2&lt;/sub&gt;&amp;alpha; (Cloprostenol) along with supportive therapies. Treatment of canine pyometra by the use of different drugs was found to be successful. Though a lower dose of cloprostenol was effective in treating pyometra, it is not recommended due to high rates of recurrence and lower conception rates. Treatment of canine pyometra using a combination of a dopamine agonist prolactin-inhibiting drug (Cabergoline) and a lower dose of synthetic PGF&lt;sub&gt;2&lt;/sub&gt;&amp;alpha; (Cloprostenol) was found to be the most effective method among the three therapeutic protocols used in the present study. &amp;nbsp;

Higher doses of cabergoline further improve metabolic parameters in patients with prolactinoma regardless of the degree of reduction in prolactin levels

Currently available studies that fully analyse the metabolic parameters in patients with prolactinoma are scarce and discordant. The aim of this study was to evaluate the metabolic effects of cabergoline (CAB) treatment in patients with newly diagnosed prolactinoma in relation to disease control and CAB dosage. This is a retrospective clinical-based therapy analysis. Forty-three patients with prolactinoma (eight men, 35 women), aged 33·65 ± 11·23 years, were evaluated metabolically at baseline and after 12 months of CAB treatment. Body mass index (BMI), systolic and diastolic blood pressure, waist circumference (WC), lipid profile, haemoglobinA1c (HbA1c), glucose and insulin levels (and their areas under the curve, AUC) after an oral glucose tolerance test, homoeostasis model assessment of insulin resistance (Homa-IR) index, insulin sensitivity index (ISI) Matsuda, oral disposition index (DIo) and visceral adiposity index (VAI) were measured at baseline and after 12 months of treatment. Twelve months of CAB reduced WC (P < 0·001), total (P = 0·001) and low-density lipoprotein \terol (P < 0·001), triglycerides (P = 0·024), fasting insulin (P < 0·001), AUCINSULIN (P < 0·001), HbA1c (P = 0·022), Homa-IR (P < 0·001) and VAI (P < 0·001), with a concomitant increase in high-density lipoprotein cholesterol (P < 0·001) and in ISI Matsuda (P < 0·001), regardless of the degree of reduction in prolactin levels. The patients receiving higher doses (>0·50 mg/week) of CAB showed lower BMI (P = 0·009), fasting insulin (P = 0·001), Homa-IR (P < 0·001) and VAI (P = 0·018) and higher ISI Matsuda (P = 0·002) and DIo (P = 0·011), compared with those on lower doses. A significant metabolic improvement was observed in patients with prolactinoma after 12 months of CAB treatment, especially when higher doses were used, highlighting the importance of considering the metabolic profile in these patients and the role of active treatment with high CAB doses.

Dopamine D2 Receptor Modulation of Human Response Inhibition and Error Awareness

Response inhibition, comprising action cancellation and action restraint, and error awareness are executive functions of considerable clinical relevance to neuropsychiatric disorders. Nevertheless, our understanding of their underlying catecholamine mechanisms, particularly regarding dopamine, is limited. Here, we used the dopamine D2 agonist cabergoline to study its ability to improve inhibitory control and modulate awareness of performance errors. A randomized, double-blind, placebo-controlled, crossover design with a single dose of cabergoline (1.25 mg) and placebo (dextrose) was employed in 25 healthy participants. They each performed the stop-signal task, a well-validated measure of action cancellation, and the Error Awareness Task, a go/no-go measure of action restraint and error awareness, under each drug condition. Cabergoline was able to selectively reduce stop-signal RT, compared with placebo, indicative of enhanced action cancellation (p < .05). This enhancement occurred without concomitant changes in overall response speed or RT variability and was not seen for errors of commission on the Error Awareness Task. Awareness of performance errors on the go/no-go task was, however, significantly improved by cabergoline compared with placebo (p < .05). Our results contribute to growing evidence for the dopaminergic control of distinct aspects of human executive ability, namely, action cancellation and error awareness. The findings may aid the development of new, or the repurposing of existing, pharmacotherapy that targets the cognitive dysfunction of psychiatric and neurological disorders. They also provide further evidence that specific cognitive paradigms have correspondingly specific neurochemical bases.

Investigation of impulsivity in patients on dopamine agonist therapy for hyperprolactinemia: a pilot study

The use of dopamine agonists (DAs) has been associated with increased impulsivity and impulse control disorders in several diseases, including Parkinson's disease. Such an effect of DAs on impulsivity has not been clearly characterized in hyperprolactinemic patients, where DAs are the mainstay of therapy. We studied the effects of DAs on impulsivity in hyperprolactinemic patients treated at a tertiary pituitary center, using validated psychometric tests. Cross-sectional study. Impulsivity was evaluated in 30 subjects, 10 hyperprolactinemic patients on DAs compared to two control groups; one comprising untreated hyperprolactinemic patients (n = 10) and a second group consisting of normoprolactinemic controls with pituitary lesions (n = 10). Measures of impulsivity included both self-report questionnaires as well as laboratory-based tasks. Hyperprolactinemic patients on DAs had a higher score (mean ± SD) in one self-report measure of impulsivity, the attention subscale of the Barratt Impulsiveness Scale (16.2 ± 2.7), as compared to the hyperprolactinemic control group (12.3 ± 2.5) and the normoprolactinemic group (14.7 ± 4.4) (p = 0.04). No statistically significant difference was found between groups with regards to the other impulsivity scales. In the DA-treated group, a correlation was observed between increased impulsivity (as assessed in the Experiential Discounting Task) and higher weekly cabergoline dose (r(2) = 0.49, p = 0.04). The use of DAs in hyperprolactinemic patients is associated with an increase in one aspect of impulsivity. This effect should be further characterized in larger, longitudinal studies.

Invasive Giant Prolactinoma Presenting as a Nasal Polyp

A previously healthy, 14-year-old obese boy (body mass index 33 kg/m2) presented with progressive weight gain, nasal stuffiness, snoring, and a polypoid mass in his left nostril. Imaging studies revealed a homogenously enhancing mass extending from the floor of sella to the nasopharynx, measuring 8.7 × 7.6 cm transversely, 9.9 × 5.4 cm sagittally, and 5.5 × 8.0 cm coronally. The mass occupied the entire nasopharynx and extended bilaterally into inferior orbital fissures and pterygopalatine fossae (Figure). It abutted the basilar artery, temporal lobe parenchyma, and the inferior margin of the sella turcica, and it elevated the anterior pituitary lobe. It also invaded the cavernous sinuses, clivus, and sphenoid bones. The initial prolactin level was markedly elevated at 29 415 ng/mL (normal range 3-18). Biopsy was consistent with pituitary adenoma, with further staining confirming it to be a prolactinoma. His prolactin level was reduced to 12 059 ng/mL while on cabergoline, 0.5 mg/wk for 2 weeks, and subsequently to a present value of 316 ng/mL, on a cabergoline dose of 12 mg/wk. There has also been a significant reduction in the tumor size in 5 years (Figure). Invasive giant prolactinomas present with extrasellar extension and massive serum prolactin elevations.1Symon L. Jakubowski J. Kendall B. Surgical treatment of giant pituitary adenomas.J Neurol Neurosurg Psychiatry. 1979; 42: 973-982Crossref PubMed Scopus (111) Google Scholar Giant prolactinomas (≥4 cm) constitute only 0.5%-4.4% of all pituitary tumors.2Corsello S.M. Ubertini G. Altomare M. Lovicu R.M. Migneco M.G. Rota C.A. et al.Giant prolactinomas in men: efficacy of cabergoline treatment.Clin Endocrinol (Oxf). 2003; 58: 662-670Crossref PubMed Scopus (101) Google Scholar, 3Shrivastava R.K. Arginteanu M.S. King W.A. Post K.D. Giant prolactinomas: clinical management and long-term follow up.J Neurosurg. 2002; 97: 299-306Crossref PubMed Scopus (128) Google Scholar, 4Yu C. Wu Z. Gong J. Combined treatment of invasive giant prolactinomas.Pituitary. 2005; 8: 61-65Crossref PubMed Scopus (35) Google Scholar Clinical and imaging in our case raised the suspicion of nasopharyngeal carcinoma, rhabdomyosarcoma, small round blue cell tumor, and esthesioneuroblastoma. This case highlights the importance of assessing serum prolactin in erosive skull base tumors, as prolactinomas respond to cabergoline obviating the need for extensive surgical resection.

Prolactinomas resistant to standard doses of cabergoline: a multicenter study of 92 patients

Dopamine agonist resistance in prolactinoma is an infrequent phenomenon. Doses of cabergoline (CAB) of up to 2.0 mg/week are usually effective in controlling prolactin (PRL) secretion and reducing tumor size in prolactinomas. The clinical presentation, management, and outcome of patients that are not well controlled by such commonly used doses of CAB-resistant patients are poorly understood. A multicenter retrospective study was designed to collect a large series of resistant prolactinoma patients, defined by uncontrolled hyperprolactinemia on CAB ≥2.0 mg weekly. Ninety-two patients (50 F, 42 M) were analyzed. At diagnosis, most had macroprolactinomas (82.6%); males were significantly older than females (P=0.0003) and presented with a more aggressive disease. A genetic basis was identified in 12 patients. Thirty-six patients (39.1%) received only medical therapy, most underwent surgery (60.9%, including multiple interventions in 10.9%), and 14.1% received postoperative radiotherapy. Eight patients developed late CAB resistance (8.7%). The median maximal weekly dose of CAB (CAB(max/w)) was 3.5 mg (2.0-10.5). Despite a higher CAB(max/w) in patients treated with multimodal therapy (P=0.003 vs exclusive pharmacological treatment), a debulking effect of surgery was shown in 14 patients, with a higher rate of PRL control (P=0.006) and a significant reduction in CAB(max/w) (P=0.001) postoperatively. At last follow-up (median 88 months), PRL normalization and tumor disappearance were achieved in 28 and 19.9% of the patients respectively, with no significant sex-related difference observed in CAB(max/w) or disease control. Mortality was 4.8%, with four patients developing aggressive tumors (4.3%) and three a pituitary carcinoma (3.3%). CAB-resistant prolactinomas remain a serious concern. Surgical debulking, newer therapeutic strategies, and early diagnosis of genetic forms could help to improve their outcome.

No clinically significant valvular regurgitation in long‐term cabergoline treatment for prolactinoma

An association between treatment for Parkinson's disease with certain dopaminergic drugs and development of cardiac valve impairment has been reported. Recent studies in hyperprolactinaemic patients treated with cabergoline (CAB) have shown either no significant findings or mild tricuspid regurgitation. To determine the prevalence of cardiac valve dysfunction in patients with hyperprolactinaemic conditions chronically treated with CAB or bromocriptine (BR). Retrospective, multicentric, cross-sectional study of cases vs controls. Eighty-three hyperprolactinaemic patients (15 men, 68 women aged 16·7-63 years; 64% microprolactinomas, 28% macroprolactinomas and 8% other etiologies) from three Spanish university hospitals chronically treated with BR (14-562·5 weeks, cumulative dose 5603 ± 7729 mg) or CAB (12-765 weeks, 217·4 ± 306·6 mg). Transthoracic echocardiographic assessment of valvular regurgitation and thickening, mitral valve tenting area and left-ventricular ejection fraction from 83 patients were compared with results from 58 age- and sex-matched controls and correlated with cumulative doses of dopaminergic drugs. No significant differences in valvular regurgitation, valve thickness or any other echocardiographic parameter were observed between controls and patients, except for 15 patients in the higher quartile of CAB cumulative dose (>180 mg), with increased prevalence of mild tricuspid regurgitation (6/15, 40% vs 8/58, 13·8%, P = 0·024; OR 4·1; 1·1-14·9). High BR cumulative dose was associated with no significant findings. No increased valvular involvement was found after long-term dopaminergic therapy for hyperprolactinaemia except for a significant increase in mild tricuspid regurgitation associated with high cumulative doses of CAB; BR seems spared from this adverse effect, although the low number of cases limits this analysis. Cumulative dose registry and long-term studies are warranted to definitely clarify this item.

Safety of Cabergoline in the Management of Pituitary Prolactin-Induced Symptoms with Patients Treated with Atypical Neuroleptics

Atypical antipsychotic-induced hyperprolactinemia can cause important clinical symptoms, particularly in young women and also in men, such as impotence, loss of libido, gynecomastia, anovulation and galactorrhea. Observational over one-year follow-up of six patients (four women and two men, mean age of 31.1 years, range 26-37), treated with different atypical antipsychotics in an outpatient psychiatric device, who had clinical complications associated to high prolactin serum levels. All of them were treated with standard doses of cabergoline. Most patients experienced significant clinical improvement after treatment with standard doses of cabergoline (mean dosage 1.08 mg/week), maintained for a mean of 18 month. Normal prolactin levels were achieved after the first months of treatment with cabergoline. No side effects or worsening of psychotic or behavioral symptoms were observed. Long-term treatment with cabergoline seems to be safe in atypical antipsychotic-treated patients.

2012 update in the treatment of prolactinomas

New information has been provided over the last years regarding treatment of prolactinomas and will be reviewed in this update. Medical treatment with a dopamine agonist (DA) remains the cornerstone of therapy and cabergoline is the first choice, due to its high efficacy and good tolerability profile. Prolonged remission after discontinuation of DA may be observed if treatment has been given for at least two years, normal prolactin has been obtained with a low dose and tumoral diameter has been reduced by at least 50%. Although the risk of restrictive cardiac valve disease is low at the standard doses of cabergoline used for the treatment of hyperprolactinaemia, long-term echocardiographic surveillance is however indicated, in particular in resistant patients who need higher doses of cabergoline (2.0mg/week or more). Neurosurgical treatment of prolactinomas is less effective than medical therapy and recurrence of hyperprolactinaemia is frequent. Besides classical indications such as drug intolerance, resistance or acute complications, new indications have emerged such as young patients with a high likelihood of complete tumour resection and who do not wish to take prolonged medical treatment, or patients who require high doses of cabergoline, in whom surgical debulking may significantly improve postoperative hormonal control. Finally, recent data indicate that cabergoline is safe for the developing foetus and for the mother, and therefore should not be preventively withdrawn in a young woman wishing to become pregnant.

Efficacy and safety of rapid escalation of cabergoline in comparison to conventional regimen for macroprolactinoma: A prospective, randomized trial

Introduction:Cabergoline (CAB) is conventionally started at a dose of 0.25-0.5 mg once a week with dose escalation at 1to 3months intervals. Previously, we and others have shown that rapid escalation and high doses of CAB can lead to normalization of serum PRL as early as 8.2 weeks in 93% of the patients. We hypothesize that rapid escalation of CAB doses, may help in both the earlier normalization of PRL and also significant shrinkage of tumor mass.Study Design:Randomized, prospective, interventional trial.Subjects and Methods:Forty two patients (male or female) with macroprolactinoma were randomized to conventional (group A) or rapid escalation (group B) of CAB dosing. In group B, CAB was started at a dose of 0.5 mg twice a week followed by a weekly hike of 1 mg/week, based on serum PRL and then monthly. The end point of the present study was a composite of normoprolactinemia and tumor shrinkage ≥50% from baseline. PRL and visual field analysis (weekly), other hormonal work up periodically and magnetic resonance imaging (sella) was performed monthly.Results:A total of 19 patients in each group completed a minimum follow-up of 6 months. There was a reduction of 72.7 ± 26.2% in group A and 84.1 ± 15.0 in group B (P = 0.24) within a week of CAB therapy. The duration of CAB treatment to normalize PRL was 10.2 ± 9.2 week(2-36) in group A and 7.2 ± 6.2 weeks(1-24) in group B (P = 0.28). There was no difference in the tumor shrinkage in either of the groups (92.3% [46.7-100%] in group A and 90.5% [66.6-100%] reduction in group B). The composite end point was achieved in 14 patients in group A (73.6%) and 16 patients in group B (84.2%) (P = 0.69). The composite end point was achieved in 13.1 ± 9.5 weeks (group A) versus 16.5 ± 14.1 weeks (group B) (P = 0.61).Discussion:This is first head to head comparative trial showing that a rapid hike of CAB dose is not associated with earlier normalization of PRL or reduction in tumor volume as compared to conventional monthly hike. There is no difference in the number of patients or duration required to achieve the composite end point. We obtained much earlier PRL normalization (8.4 weeks) as compared to previous studies (36-72 weeks), probably because PRL was not assessed as frequently as in the present study. Rapid escalation of CAB was well tolerated.Conclusion:A weekly or a conventional 4 weekly escalation of CAB have a similar efficacy with regards to the achievement of normoprolactinemia and significant tumor shrinkage for macroprolactinoma.

Giant prolactinoma: Where's the prolactin?

A 22-year-old man presented to the emergency department ith intermittent headaches after striking his head on a car door ue to decreased peripheral vision. Upon questioning, he related a 6 onth history of weakness as well as a decrease in libido and beard rowth. There was no family history of pituitary or endocrine neolasia. Physical findings included bitemporal hemianopsia, optic trophy, galactorrhea, and testicular atrophy. MRI of the pituitary evealed a 5.8 × 3.7 × 3.0 cm sellar/suprasellar mass extending into he cavernous sinus, the right lateral ventricle with associated latral horn dilatation, and the left sphenoid and ethmoidal sinuses Fig. 1A). Laboratory investigations revealed an extremely elevated rolactin level of 5474 g/L, hypogonadotrophic hypogonadism, ow IGF-1 levels, low-normal thyroid hormone levels and an adeuate morning cortisol level (Table 1). Treatment was initiated with bromocriptine 5 mg twice daily. is prolactin level dropped to 23 g/L over the next 2 weeks. hree months later, his prolactin level rose to 138 g/L. Repeated RI indicated the mass was smaller at 4.6 × 2.5 × 1.5 cm (Fig. 1B). reatment was switched to cabergoline 0.5 mg twice weekly. Two onths later, because the prolactin level had only dropped to 11 g/L, the cabergoline dose was increased to 1 mg twice weekly. owever, since the bitemporal hemianopsia and optic atrophy had

A case of an ectopic prolactinoma

A 34-year-old female presented to our clinic with a 1.5 year history of secondary amenorrhea and galactorrhea. Prolactin (PRL) level was found to be 151.89 ng/ml. Pituitary imaging was reported to be normal. An examination of the patient revealed that PRL level was still high so the dose of cabergoline was further increased and subsequently, bromocriptine was added to the treatment. There was no reduction in PRL levels in controls. A scanning was performed to look for an ectopic focus. Abdominal computerized tomography revealed a heterogenous mass lesion originating from the uterus. Octreotide scintigraphy was performed and we observed an involvement consistent with the mass in the uterus. The patient underwent abdominal total hysterectomy. PRL dropped to 0.4 ng/ml the next day after the operation. The pathology result was a low-grade malignant mesenchymal tumor. Prolactin was found to be immunohistochemically negative. However, galactorrhea disappeared postoperative and PRL levels are still low. Elevated levels of PRL, resistant to bromocriptine and cabergoline, rapidly returned to normal after hysterectomy, which obviously indicates that hyperprolactinemia was associated with the myoma of the uterus.

Reversible cardiac valve fibrosis secondary to treatment with high-dose cabergoline for Parkinson’s disease

When first presenting in June 2006 at the movement disorders clinic, the patient, a 51-year-old gentleman, was under treatment with cabergoline after having been diagnosed with Parkinson’s disease (PD) of the akinetic rigid type 2 years ago. He was in good state of health, but he complained about progressive shortness of breath when climbing stairs, which had started a few weeks previously. On auscultation, a 3/6 diastolic murmur was noted in the aortal valve area. An immediately performed echocardiography showed fibrosis and thickening of the tricuspid, mitral and aortic valves, a second-grade insufficiency of the mitral and aortic valves and a borderline size of the left ventricle (Fig. 1). The patient reported that he had gradually increased his dose of cabergoline to 26 mg/day within the past year without approval of his treating neurologist. He did so in order to minimize the impact of motoric limitations due to PD and to be able to participate in the local tennis championships. This dose enabled him to perform at the same level as before the diagnosis of PD. Cabergoline was discontinued instantly and replaced by levodopa and amantadine. In summary, he had taken a cumulative dose of 8,353 mg cabergoline since the therapy had been initiated 20 months before. In July 2005, 1 year before presentation at the movement disorders clinic, echocardiography was performed. The daily dose of cabergoline at that time was 4 mg/day. A prolapse of the anteromedial leaflet of the mitral valve was noted, otherwise the examination was unremarkable. Based on this study, continuation of the therapy with cabergoline was assessed to be safe. The course of the cardiac examinations is shown in Fig. 1. Despite discontinuation of cabergoline, echocardiography showed a deterioration of the affected valves in November 2006 and February 2007. Along with these echocardiographical findings the clinical condition of the patient worsened until February 2007, when he reported progressive dyspnoea when climbing stairs. At this time complete invasive cardiac evaluation including aortography, ventriculography and coronary angiography confirmed the echocardiographic diagnosis. Based on severity of symptoms (NYHA III), and based on the diagnostic findings, surgical replacement of the aortic and mitral valves was recommended. However, the patient insisted to remain on conservative therapy including frequent re-evaluations of his cardiac condition. In April 2008 the patient reported having recovered from the shortness of breath when climbing stairs and echocardiography was significantly improved (Fig. 1). By December 2009, echocardiography showed a continued improvement, which was accompanied by an almost complete recovery of his physical condition allowing the patient to start playing tennis again. Because of cardiac side effects, ergot-type dopamine agonists are no longer considered as first line treatment of PD [1–5]. However, the incidence of dopamine agonists induced cardiac fibrosis remains under discussion [3]. The excessive dose of cabergoline in our case suggests a dose dependent effect on the development of cardiac fibrosis, which has been suggested for pergolide before [6]. The pathogenic mechanism of cardiac valve fibrosis involves the stimulation of 5-HT2b receptors by dopamine J. Levin K. Botzel (&) Department of Neurology, Ludwig-Maximilians University Munich, Marchioninistr. 15, 81377 Munich, Germany e-mail: kboetzel@med.uni-muenchen.de